BACKGROUND: SGLT2 inhibitors are a new class of oral antidiabetics prescribed in the United States since 2013. They act by inhibiting reabsorption of glucose in the proximal convoluted tubule of the kidney, allowing excess glucose to be excreted. Little has been reported regarding effects of non-therapeutic exposure to this class of medication. METHODS: Retrospective records from 13 poison centers were examined for human exposures to SGLT2 inhibitors between 1st January 2013 and 31st December 2016...

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...

Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...

AIMS/INTRODUCTION: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis-induced hypoglycemia has not yet been examined in detail. The aim of the present study is to investigate the mechanisms underlying hypoglycemia in sepsis. MATERIALS AND METHODS: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test (PTT)...

OBJECTIVE: It was uncertain whether an algorithm that involves increasing insulin dosages by 1 unit/day may cause more hypoglycemia with the longer-acting insulin glargine 300 units/mL (GLA-300). The objective of this study was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in people with uncontrolled type 2 diabetes mellitus, mainly in a primary care setting. METHODS: This was a 12-week, open-label, randomized, multicentre pilot study...

Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected β-cells from streptozotocin-induced apoptosis...

BACKGROUND: Given the prevalence of diabetes mellitus in modern society, health care providers are frequently tasked with managing glucose control in the perioperative period. When determining perioperative diabetes management, the clinician must balance the need to maintain relative euglycemia at the time of surgery with preventing hypoglycemia or hyperglycemia in a fasting surgical patient. This balance requires an understanding of the pharmacology of these medications, the type of surgery, and the patient's degree of diabetic control...

Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis...

Objective: To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods: A total of 41 338 women delivered in the 15 hospitals during the 6 months, 195 women with PGDM (PGDM group) and 195 women with normal glucose test result (control group) were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups...

BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...

CONTEXT AND OBJECTIVE: The prevalence and characteristics of gestational diabetes mellitus (GDM) have changed over time, reflecting the nutritional transition and changes in diagnostic criteria. We aimed to evaluate characteristics of women with GDM over a 20-year interval. DESIGN AND SETTING: Comparison of two pregnancy cohorts enrolled in different periods, in university hospitals in Porto Alegre, Brazil: 1991 to 1993 (n = 216); and 2009 to 2013 (n = 375). METHODS: We applied two diagnostic criteria to the cohorts: International Association of Diabetes and Pregnancy Study Groups (IADPSG)/World Health Organization (WHO); and National Institute for Health and Care Excellence (NICE)...

Administration of parenteral nutrition (PN) may result in hyperglycemia in patients with preexisting diabetes or disease-related insulin resistance, and it can be associated with increased rates of complications. Treatment requires insulin therapy. Insulin can be administered subcutaneously, intravenously via a variable rate sliding scale, or by adding it directly to the PN. The last method is a potentially attractive technique for a number of reasons-it could deliver the insulin intravenously at a steady rate alongside carbohydrates, and in malnourished patients with little subcutaneous tissue, it may prevent the need for frequent insulin injections...

PURPOSE: A trade-off exists in most diabetes therapies between the benefits of good glycemic control and the morbidity of hypoglycemia. Balancing these factors to achieve desired outcomes is a key consideration for personalized diabetes therapy. Hypoglycemia at night (nocturnal hypoglycemia [NH]) is a common but often under-reported problem in insulin-treated patients with type 2 diabetes. To better understand the risk for NH, we pooled data from multiple clinical trials of insulin treatment and specifically examined NH risk factors in relation to glycemic goals...

Neuregulin-1β is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs...

Measurement of insulin and its therapeutic analogs is important in diabetes, hypoglycemia, sports anti-doping and toxicology. Commercial insulin immunoassays fail to detect commonly prescribed insulin analogs. Because of their unique sequences and masses, these analogs are readily measured and distinguished with mass spectrometric (MS) assays. Reviewed here is an insulin mass spectrometric immunoassay (MSIA) that combines micro-scale immunoaffinity capture with sensitive MS detection of insulin and its therapeutic analogs...

OBJECTIVE: The aim of this meta-analysis was to determine the efficacy and safety of glyburide as a treatment for gestational diabetes mellitus (GDM) compared to insulin. METHODS: A meta-analysis was conducted to compare the management of gestational diabetes with glyburide and insulin. Studies fulfilling all of the following inclusion criteria were included in this meta-analysis: subjects were women with gestational diabetes requiring drug treatment; the comparison treatment included glyburide vs insulin; one or more outcomes (maternal or neonatal) should be provided in the individual study; the study design should be a randomized control trial...

Glycemic fluctuations, characterized by short-term oscillations in plasma glucose, are important when managing type 2 diabetes (T2D) and may be considered a target of glucose-lowering therapies. Continuous glucose monitoring (CGM) has been used to evaluate the effects of different treatments on glycemic fluctuations. This review examines approaches to and the importance of minimizing glycemic fluctuations among patients with T2D. Measures of HbA1c, fructosamine, and glycated albumin reflect a long-term average of plasma glucose, and are therefore unable to provide an accurate measure of short-term glycemic oscillations...